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A. De Lorenzo E.M. Dos Santos A.S. Bello Moreira G.V.B. Huguenin E. Tibirica 《Brazilian journal of medical and biological research》2021,54(6)
Endothelial dysfunction is a well-known component of the pathophysiology of heart failure (HF), with proven prognostic value. Dietary supplementation with whey protein (WP) has been widely used to increase skeletal muscle mass, but it also has vascular effects, which are less understood. This study aimed to evaluate the effects of WP supplementation on the systemic microvascular function of HF patients. This was a blinded, randomized, placebo-controlled clinical trial that evaluated the effects of 12-week WP dietary supplementation on systemic microvascular function, in patients with HF New York Heart Association (NYHA) classes I/II. Cutaneous microvascular flow and reactivity were assessed using laser speckle contrast imaging, coupled with pharmacological local vasodilator stimuli. Fifteen patients (aged 64.5±6.2 years, 11 males) received WP supplementation and ten patients (aged 68.2±8.8 years, 8 males) received placebo (maltodextrin). The increase in endothelial-dependent microvascular vasodilation, induced by skin iontophoresis of acetylcholine, was improved after WP (P=0.03) but not placebo (P=0.37) supplementation. Moreover, endothelial-independent microvascular vasodilation induced by skin iontophoresis of sodium nitroprusside, was also enhanced after WP (P=0.04) but not placebo (P=0.42) supplementation. The results suggested that dietary supplementation with WP improved systemic microvascular function in patients with HF. 相似文献
994.
Chronic antigen stimulation can lead to immune exhaustion (a state of T cell dysfunction). Several phenotypical signatures of T cell exhaustion have been described in various pathological situations, characterized by aberrant expression of multiple inhibitory receptors (IR). This signature has been barely studied in the context of allogenic organ transplantation. We undertook a cross-sectional analysis of the expression of IR [CD244, CD279, T cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) and CD57] and their correlation with cytokine-producing functions in T cells reconstituting after lymphocyte depletion in patients transplanted from living donors, with preformed donor-specific antibodies. After ABO incompatible transplantation, T cells progressively acquired a phenotype similar to healthy donors and the expression of several IR marked cells with increased functions, with the exception of TIGIT, which was associated with decreased cytokine production. In stark contrast, T cell reconstitution in patients with anti-human leukocyte antigen (HLA) antibodies was characterized with an increased co-expression of IR by T cells, and specifically by an increased expression of TIGIT. Furthermore, expression of these receptors was no longer directly correlated to cytokine production. These results suggest that T cell alloreactivity in HLA-incompatible kidney transplantation drives an aberrant T cell reconstitution with respect to IR profile, which could have an impact on the transplantation outcome. 相似文献
995.
Azmi Nasser Tesfaye Liranso Toyin Adewole Nicholas Fry Joseph T. Hull Fatima Chowdhry Gregory D. Busse Zare Melyan Andrew J. Cutler Robert L. Findling Stefan Schwabe 《Psychopharmacology bulletin》2021,51(2):43
Objectives:Three Phase 3 trials have demonstrated the efficacy and safety of SPN-812 in pediatric subjects with ADHD. Here, we report the results of a fourth trial.Methods:Eligible adolescent subjects (N = 297) were randomized to SPN-812 (400- or 600-mg/day) or placebo. The primary efficacy endpoint was change from baseline (CFB) at end of study (EOS) in the ADHD Rating Scale-5 (ADHD-RS-5) Total score. Statistical analyses included sequential testing for multiple treatment comparisons. Key secondary endpoints included: Clinical Global Impression-Improvement (CGI-I) score at EOS and CFB at EOS in the Conners 3–Parent Short Form (Conners 3–PS) Composite T-score and Weiss Functional Impairment Rating Scale–Parent (WFIRS–P) Total average score.Results:The CFB at EOS ADHD-RS-5 Total score (least square [LS] means ± SE) for 400-mg/day, 600-mg/day SPN-812, and placebo was −18.3 ± 1.36, −16.7 ± 1.39, and –13.2 ± 1.38, respectively. The difference vs. placebo was statistically significant only for the 400-mg/day SPN-812 treatment group (600 mg/day: p = 0.0712; 400 mg/day: p = 0.0082). Neither dose could be considered superior to placebo due to the use of statistical method of sequential testing. Significant improvements were observed on a number of secondary endpoints. SPN-812 was well tolerated at both doses, with <5% discontinuation rate due to adverse events.Conclusions:Treatment with 400- but not 600-mg/day SPN-812 resulted in statistically significant improvement in the primary endpoint. The negative result seen in the 600-mg/day SPN-812 group was likely due to an unusually high placebo response. Safety data were consistent across all doses in the SPN-812 trials. 相似文献
996.
Questions have long been used as a teaching tool by teachers and preceptors to assess students’ knowledge, promote comprehension, and stimulate critical thinking. Well-crafted questions lead to new insights, generate discussion, and promote the comprehensive exploration of subject matter. Poorly constructed questions can stifle learning by creating confusion, intimidating students, and limiting creative thinking. Teachers most often ask lower-order, convergent questions that rely on students’ factual recall of prior knowledge rather than asking higher-order, divergent questions that promote deep thinking, requiring students to analyze and evaluate concepts. This review summarizes the taxonomy of questions, provides strategies for formulating effective questions, and explores practical considerations to enhance student engagement and promote critical thinking. These concepts can be applied in the classroom and in experiential learning environments. 相似文献
997.
Olayinka Rasheed Ibrahim Bello Muhammed Suleiman Suleiman Bello Abdullahi Taofeek Oloyede Abdallah Sanda Maruf Sanusi Gbadamosi Bashir Olajide Yusuf Rabilu Yandoma Iliyasu Lawal Magaji Ibrahim Adamu Danladi Dawud Sulaiman Saidu Bashir Nwawueze Efam Okonta Wasinda Francis Umar Abiodun Gbenga Tekobo Muhammadu Sani Abubakar Bashir Taiye Aminu Shuaibu Onoruoyiza Ibrahim Rasaq Olaosebikan Olugbenga Ayodeji Mokuolu 《The American journal of tropical medicine and hygiene》2020,103(6):2376
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Clia Dupain Julien MasliahPlanchon Cline Gu Elodie Girard Pierre Gestraud Pauline Du Rusquec Edith Borcoman Diana Bello Francesco Ricci Sgolne Hescot MariePaule Sablin Patricia Tresca Alexandre de Moura Delphine Loirat Maxime Frelaut Anne VincentSalomon Charlotte Lecerf Cline Callens Samantha Antonio Coralie Franck Odette Mariani Ivan Biche Maud Kamal Christophe Le Tourneau Vincent Servois 《Molecular oncology》2021,15(1):104
High‐throughput molecular profiling of solid tumours using core needle biopsies (CNB) allows the identification of actionable molecular alterations, with around 70% success rate. Although several studies have demonstrated the utility of small biopsy specimens for molecular testing, there remains debate as to the sensitivity of the less invasive fine‐needle aspiration (FNA) compared to CNB to detect molecular alterations. We aimed to prospectively evaluate the potential of FNA to detect such alterations in various tumour types as compared to CNB in cancer patients included in the SHIVA02 trial. An in‐house amplicon‐based targeted sequencing panel (Illumina TSCA 99.3 kb panel covering 87 genes) was used to identify pathogenic variants and gene copy number variations (CNV) in concomitant CNB and FNA samples obtained from 61 patients enrolled in the SHIVA02 trial (). The main tumour types analysed were breast (38%), colon (15%), pancreas (11%), followed by cervix and stomach (7% each). We report 123 molecular alterations (85 variants, 23 amplifications and 15 homozygous deletions) among which 98 (80%) were concordant between CNB and FNA. The remaining discordances were mainly related to deletions status, yet undetected alterations were not exclusively specific to FNA. Comparative analysis of molecular alterations in CNB and FNA showed high concordance in terms of variants as well as CNVs identified. We conclude FNA could therefore be used in routine diagnostics workflow and clinical trials for tumour molecular profiling with the advantages of being minimally invasive and preserve tissue material needed for diagnostic, prognostic or theranostic purposes. NCT03084757
Abbreviations
- CNB
- core needle biopsy
- CNV
- copy number variation
- CT
- computerized tomography
- EDTA
- ethylenediaminetetraacetic acid
- FDR
- false detection rate
- FNA
- fine‐needle aspiration
- G
- Gauge
- NGS
- next‐generation sequencing
- QC
- quality control
- RPMI
- Roswell Park Memorial Institute
- SNV
- single nucleotide variation
- TSCA
- Truseq Custom Amplicon
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